Antimicrobial skin preparation

ABSTRACT

An antimicrobial skin composition comprised of an antimicrobial agent, an alcohol, one or more pH sensitive viscosity builders and water. Preferably, the viscosity builders of the present invention are comprised of pH sensitive methacrylic polymers which are alcohol compatible and have pH controlled water solubility. The composition combines the advantages of an antimicrobial agent and an alcohol, and has a viscosity of from 100 cp to 1,000. This viscosity is sufficiently low for purposes of dispensing and applying the preparation, yet sufficiently high to cause the solution to remain in the area of the wound and not flow away or pool under the patient. The preparation further forms a water-resistant film that is difficult to remove during wound irrigation, but can be easily removed upon completion of the procedure. Finally, the preparation is fast drying so as to take advantage of the fast high initial kill properties of alcohol.

BACKGROUND OF INVENTION

[0001] This invention relates to antimicrobial skin preparations. Morespecifically, it relates to PVP-I/alcohol preparations that are easy toapply but resist flow after application, are fast drying, and formwater-resistant but easily removable films.

[0002] Antimicrobial skin preparations function to reduce skin infectionin surgical and other wounds, including needle punctures. Theapplication of antimicrobial preparations to wounds has become standardpractice in hospitals, surgery centers, and medical test laboratories.This application is generally carried out through the use of swabs orsponges to deliver the liquid antimicrobial preparation to the skin. Thepreparations may be prepared for use in a pre-packaged form (i.e.,liquid and swab in a sealed package) or as a separate bottled liquid.Multiple applications of antimicrobial skin preparations are oftenrequired, with the preparation either being allowed to dry or blotteddry between applications. Since most current antimicrobial skinpreparations are water soluble, reapplication is often necessary afterthe wound is irrigated with water.

[0003] Antimicrobial skin preparations are well known in the art,including those containing iodine complexed with a polymer (iodophors).The polymer is most often polyvinyl pyrrolidone (Povidone). Iodophorpreparations typically contain about 7.51-10% by volume of the iodinecomplex; Povidone-Iodine (PVP-I) solution is one of the most widelyaccepted preoperative antimicrobials. Solutions containing 5-10% PVP-Iare generally recognized as safe. PVP-I solutions form a durable yetwater soluble antimicrobial film when dry, and therefore resistpre-mature removal while permitting easy removal with water and mildrubbing. However, most existing iodophor skin preparations arelow-viscosity liquids that tend to flow freely after application intoareas remote from the wound site. This creates a need for extra careduring application and increases the potential for irritation caused bysolution pooling under the patient. A product that eliminates the flowproblems associated with low-viscosity PVP-I solution is Povidone-Iodinegel (PVP-I gel). PVP-I gel is made by adding a cellulose gel, such ashydroxyethylcellulose, to PVP-I to greatly increase its viscosity to atleast 8,000 cp. A PVP-I solution that is gelled withhydroxyethylcellulose is detailed in U.S. Pat. No. 5,137,718. In orderto increase the initial kill of bacteria, alcohol can be added to PVP-Igel, as described in U.S. Pat. No. 5,916,882. Gelled PVP-I andPVP-I/alcohol solutions are flow-resistant compositions; however, as aresult they are more difficult to dispense and apply than a lowviscosity PVP-I solution. Furthermore, solutions in gel form dry slowly,which increases application time and reduces the benefits of the fastacting antimicrobial properties of alcohols in the PVP-I/alcohol gel.Another inherent problem with the current hydrophilic gel preparationsis that they are water-soluble and therefore readily rehydrate duringwound irrigation or subjection to water-containing body fluids, causingpremature removal of the film and interference with surgical drapeadhesion during surgical procedures.

[0004] Water-resistant films are disclosed in U.S. Pat. Nos. 6,228,354,5,922,314 and 4,584,192, but the skin preparations that produce thesefilms are low-viscosity and suffer from the flow/pooling problemsdiscussed above. The PVP-I/alcohol solution disclosed in U.S. Pat. No.6,228,354 has a faster drying time than the PVPI/alcohol gel, thustaking full advantage of the fast acting antimicrobial properties ofalcohol in conjunction with PVP-I. The solution further eliminatesinterference with surgical drape adhesion caused by gel, and hascontrolled moisture resistance thereby reducing the likelihood ofpremature removal by irrigation during procedures. However, in additionto its low viscosity, the film can only be removed with an aqueousalkaline solution and physical rubbing. Similarly, the composition ofU.S. Pat. No. 4,584,192 is resistant to removal with water, and can onlybe removed by certain alcohols which irritate compromised skin.

[0005] Finally, most prior art antimicrobial skin preparations use wateras a solvent, which slows their drying rate, resulting in slow filmformation, flow away from the wound site, and lengthened applicationprocess time.

[0006] It would be beneficial to have an antimicrobial skin preparationcombining the advantages of an antimicrobial agent and an alcohol, whichpreparation has sufficiently low viscosity for ease of dispensing andapplication, yet sufficiently high viscosity to cause the solution toremain in the area of the wound and not flow away or pool under thepatient; which forms a water-resistant film that is difficult to removeduring wound irrigation, but can be easily removed upon completion ofthe procedure; and which is fast drying so as to take advantage of thefast high initial kill properties of alcohol, limit flow away from thewound site, and decrease application time. Prior to this invention, nosingle product has been developed to combine the advantages of thevarious current antimicrobial skin preparations as discussed above.

SUMMARY OF INVENTION

[0007] The present invention is an antimicrobial skin preparation havinga viscosity of 100 cp to 1000 cp, combining the advantages of anantimicrobial agent and an alcohol. This viscosity level is sufficientlylow to allow for easy application and dispensation, but sufficientlyhigh to cause the solution to remain in the area of the wound and notflow away from the prep site or pool under the patient. The viscositymeasurements referred to above are made at 25° C. with a BrookfieldViscometer Model LVF, using spindle 2 at 30 rpm.

[0008] The solution of the present invention further forms awater-resistant film that is difficult to remove during woundirrigation, and has comparable low potential for rehydration orinterference with surgical drape adhesion as standard PVP-I solutions.However, the solution can be easily removed upon completion of theprocedure with water and moderate rubbing.

[0009] Additionally, the solution of the present invention is fastdrying so as to take advantage of the fast high initial kill propertiesof alcohol, limit flow away from the wound site, and decreaseapplication time.

[0010] The solution is further formulated to provide a high level ofefficacy with minimum required active concentration, thus reducingsolution cost and minimizing irritation. The solution is effective andsafe for use on intact skin in single step preparation of phlebotomy,I.V., and surgical sites.

[0011] The antimicrobial skin composition of the present invention iscomprised of an antimicrobial agent, an alcohol, one or more pHsensitive viscosity builders and water. Surfactants, skin irritationreducers, and buffers may also be included. The active ingredients ofthe present invention are generally recognized as safe. The use of a pHsensitive viscosity builder eliminates the slow drying and re-hydrationproblems associated with gel forms of PVP-I and PVP-I/alcoholpreparations.

DETAILED DESCRIPTION

[0012] The antimicrobial skin composition of the present invention iscomprised of, in its most general form, an antimicrobial agent, analcohol, one or more pH sensitive viscosity builders and water.Preferably, the antimicrobial agent is complexed with a polyvinyllactam, and more preferably the antimicrobial agent constitutes PVP-I.Suitable alcohols for the solution of the present invention include butare not limited to ethanol and isopropanol. Isopropanol is preferred, asit is more efficient than ethanol in dissolving skin oils.

[0013] The viscosity builders in the solution are alcohol compatible andhave pH controlled water solubility, and are preferably methacrylicpolymers. The preferred viscosity builders include acidic acrylicpolymers such as Acrylates/C10-30 Alkyl Acrylate Crosspolymer,Acrylates/Beheneth-25 Methacrylate Copolymer, Acrylates Copolymer,Acrylates/Steareth-20 Methacrylate Copolymer and Carbomer. A morepreferred viscosity builder is the Acrylates/Steareth-20 MethacrylateCopolymer, which is available under the trade name of Aculyn 22 fromRohm and Haas. Aculyn 22 is supplied by Rohm and Haas at a polymersolids concentration of 30%, with a pH of about 3.0. Acidic acrylicpolymers normally function as viscosity builders that become morewater-soluble as they are neutralized; the water solubility thereof islimited in the present invention because of the relatively low pH of thesolution. While the polymer is insoluble in water at low pH, it iscompatible with alcohol regardless of the pH level thereof, andtherefore the polymer is especially suitable in the low pH solution ofthe present invention. Furthermore, viscosity builders having pHcontrolled water solubility decrease the water solubility of the prepfilm of the present invention, but allow for easy removal by mildphysical rubbing. The main mechanism of Aculyn 22 in building viscosityfor the solution of the present invention is its associative thickeningproperties, caused by physical forces between particles of Aculyn 22 andthe solution.

[0014] Preferably, the solution contains 5-10% by weight complexedantimicrobial agent, 60-95% by volume alcohol, 1-5% by solids weightpolymer pH sensitive viscosity builder, and water. As regards thealcohol, when using ethanol it should comprise about 60-95% of thevolume of the entire solution, whereas isopropanol should comprise about70-91.3% of the volume of the entire solution. The preferred solutionhas a pH range from about 1.5 to 6.5, and a specific gravity range ofabout 0.790 to 0.990 depending upon the applicable concentrations of theactives and excipient, if any. The solution of the present invention mayalso include a skin irritation reducer (e.g., glycerin), a surfacetension adjuster (e.g., a nonionic surfactant such as Nonoxynol-9), asynergistic secondary thickener (e.g., polyvinyl pyrrolidone), acid andbase pH adjusters (e.g., phosphoric acid and aminomethyl propanol),buffers and/or additional viscosity builders.

[0015] A more preferred embodiment of the invention includes about 5-10%by weight PVP-I; about 70-91% by volume isopropanol; about 0.2%-0.3% byweight aminomethyl propanol; about 0.01% to 1.0% by weight phosphoricacid; 0.1%-5% by weight glycerin; 0.1% to 1.0% by weight non-ionicsurfactant Nonoxynol-9; and 2%-4% pH sensitive methacrylic polymerviscosity builder selected from acidic acrylate polymers which arecommonly used as viscosity builders.

[0016] A final preferred antimicrobial skin preparation embodiment ofthe present invention comprises, by weight: 7.5% PVP-I, 0.75% availableiodine (USP/EP Grade); 64.5% isopropanol (USP/EP Grade); 2.4%Acrylates/Steareth-20 Methacrylate Copolymer; 0.27% aminomethyl propanol95%; 0.06% phosphoric acid (75%); and water. The pH of this preferredembodiment of the present invention is approximately 3.5, the viscosityis approximately 250 cp, and the specific gravity is approximately0.889.

[0017] The composition of the present invention is preferablymanufactured by combining a minimal amount of the alcohol and sufficientamount of the water to provide volume to blend in the antimicrobialagent, if the same is provided in powdered form. As there is some riskof ignition of suspended dust particles when adding a powderedantimicrobial agent, the preliminary alcohol content should be minimaland the dust particles should be added to avoid forming a cloud offinely dispersed particles over the batch. The viscosity builder is thenpreferably diluted in water and added slowly to the solution. Anyadditional alcohol can then be added to the solution, as well as anydesirable elements such as glycerin and base pH adjusters. Each elementshould be added slowly, and mixed well into the solution so that thesolution is homogeneous prior to the addition of a subsequent element.

1. An antimicrobial skin composition comprised of an antimicrobialagent, an alcohol, one or more pH sensitive viscosity builders andwater.
 2. The composition of claim 1, whereby the composition has aviscosity of between about 100 cp to 1,000 cp.
 3. The composition ofclaim 2, whereby the antimicrobial agent is complexed with a polyvinyllactam.
 4. The composition of claim 3, whereby the antimicrobial agentis Iodine and the polyvinyl lactam is polyvinyl pyrrolidone.
 5. Thecomposition of claim 2, whereby the alcohol is chosen from the groupcomprising ethanol or isopropanol.
 6. The composition of claim 2,whereby the viscosity builders are pH sensitive methacrylic polymers. 7.The composition of claim 6, whereby the pH sensitive methacrylicpolymers are chosen from the group comprising: Acrylates/C10-30 AlkylAcrylate Crosspolymer, Acrylates/ Beheneth-25 Methacrylate Copolymer,Acrylates Copolymer, Acrylates/Steareth-20 Methacrylate Copolymer andCarbomer.
 8. The composition of claims 1, 2, 4, or 5, whereby theviscosity builder is Acrylates/Steareth-20 Methacrylate Copolymer. 9.The composition of claims 1 or 2, whereby at least one of the viscositybuilders has associative thickening properties within the solution. 10.The composition of claim 8, further comprising a skin irritationreducer.
 11. The composition of claim 8, further comprising a surfacetension adjuster.
 12. The composition of claim 8, further comprisingbuffers.
 13. The composition of claim 8, further comprising pHadjusters.
 14. The composition of claim 8, wherein the viscosity of thecomposition is between 150 cp and 700 cp.
 15. The composition of claim8, wherein the viscosity of the composition is between 200 cp and 400cp.
 16. The composition of claim 8, whereby the pH of the composition isfrom about 1.5 to 6.5.
 17. An antimicrobial skin composition comprisedof (a) 5-10% by weight antimicrobial agent complex, (b) 60-95% by volumealcohol, (c) 1-5% by solids weight polymer viscosity builder, (d) andwater.
 18. The composition of claim 17, whereby the antimicrobial agentcomplex is Povidone Iodine, and the alcohol is isopropanol and iscontained at 70-91.3% by volume.
 19. The composition of claims 17 or 18,whereby the viscosity builder is Acrylates/Steareth-20 MethacrylateCopolymer.
 20. The composition of claim 17, wherein the viscosity of thecomposition is between 150 cp and 700 cp.
 21. The composition of claim19, wherein the viscosity of the composition is between 200 cp and 400cp.
 22. An antimicrobial skin composition having a viscosity of between100 cp and 1,000 cp, comprised of: (a) 5-10% by weight Povidone Iodine,(b) 70-91% by volume isopropanol, (c) 1-5% by solids weight polymerviscosity builder, and (d) water.
 23. The antimicrobial skin compositionof claim 22, further comprising about 0.2%-0.3% w/w aminomethylpropanol; about 0.01% to 1.0% w/w phosphoric acid; 0.1%-5% w/w glycerin;0.1 to 1.0% w/w non-ionic surfactant Nonoxynol-9.
 24. An antimicrobialskin composition comprised of (a) 7.5% by weight Povidone Iodine, (b)70-91% by volume isopropanol, (c) 2.4% by weight Acrylates/Steareth-20methacrylate copolymer, (d) 0.27% by volume aminomethyl propanol (95%),(e) 0.06% by volume phosphoric acid (75%) and (f) water.
 25. Thecomposition of claim 24, whereby the pH of the composition isapproximately 3 to 4 and the viscosity is approximately 200 to 300 cp.